ACH-1625 is a linear peptidomimetic inhibitor that non-covalently binds to hepatitis C virus (HCV) NS3 protease with high potency and specificity. Short term monotherapy of HCV genotype-1 (GT-1) infection with ACH-1625 was found to be safe and resulted in ≥3.3 log(10) IU/mL mean viral load reduction. This viral load decay data was analyzed to compare HCV dynamics with prior reports and estimate the antiviral efficiency of ACH-1625.

METHODS:

Drug efficiency (ε) was estimated by analyzing the viral decay following initiation of up to 5 days of monotherapy with ACH-1625 in 36 chronically-infected HCV GT-1 patients. During this monotherapy study, ACH-1625 was administered either twice a day for 4.5 days or once daily for 5 days at 5 different dose levels in 36 patients.

RESULTS:

A sharp viral decay during first 48 hours following the initiation of ACH-1625 treatment afforded high drug efficiency estimates (≥ 0.9934). In addition, an increase in the estimated drug efficiency was observed with increasing ACH-1625 dose. The observed anti-HCV response was fairly uniform in this proof-of-concept study across the population of 36 patients.

CONCLUSIONS:

Estimates of the treatment independent viral kinetics parameters were consistent with prior reports and the estimated drug efficiency of ACH-1625 monotherapy was very high (≥0.9934) in fasted and fed states.